Stereotactic radiosurgery for medically refractory non-lesional epilepsy: A case-based Radiosurgery Society (RSS) practice review.

INTRODUCTION: Medically refractory epilepsy (MRE) occurs in about 30 % of patients with epilepsy, and the treatment options available to them have evolved over time. The classic treatment for medial temporal lobe epilepsy (mTLE) is anterior temporal lobectomy (ATL), but an initiative to find less invasive options has resulted in treatments such as neuromodulation, ablative procedures, and stereotactic radiosurgery (SRS). SRS has been an appealing non-invasive option and has developed an increasing presence in the literature over the last few decades. This article provides an overview of SRS for MRE with two example cases, and we discuss the optimal technique as well as the advantages, alternatives, and risks of this therapeutic option. CASES: We present two example cases of patients with MRE, who were poor candidates for invasive surgical treatment options and underwent SRS. The first case is a 65-year-old female with multiple medical comorbidities, whose seizure focus was localized to the left temporal lobe, and the second case is a 19-year-old male with Protein C deficiency and medial temporal lobe sclerosis. Both patients underwent SRS to targets within the medial temporal lobe, and both achieve significant improvements in seizure frequency and severity. DISCUSSION: SRS has generally been shown to be inferior to ATL for seizure reduction in medically refractory mTLE. However, there are patients with epilepsy for which SRS can be considered, such as patients with medical comorbidities that make surgery high risk, patients with epileptogenic foci in eloquent cortex, patients who have failed to respond to surgical management, patients who choose not to undergo surgery, and patients with geographic constraints to epilepsy centers. Patients and their physicians should be aware that SRS is not risk-free. Patients should be counseled on the latency period and monitored for risks such as delayed cerebral edema, visual field deficits, and radiation necrosis.

Radiosurgery Society Case-Based Guide to Stereotactic Body Radiation Therapy for Challenging Cases of Spinal Metastases.

PURPOSE: Spinal stereotactic body radiation therapy (SBRT) has become the standard of care in management of patients with limited sites of metastatic disease, radio-resistant histologies, painful vertebral metastases with long life expectancy and cases of reirradiation. Our case-based guidelines aim to assist radiation oncologists in the appropriate utilization of SBRT for common, yet challenging, cases of spinal metastases. MATERIALS AND METHODS: Cases were selected to include scenarios of large volume sacral disease with nerve entrapment, medically inoperable disease abutting the thecal sac, and local failure after prior SBRT. Relevant literature was reviewed, and areas requiring further investigation were discussed to offer a framework for evidence-based clinical practice. RESULTS: Spinal SBRT can be effectively delivered in challenging cases following multidisciplinary discussion by utilizing a methodical approach to patient selection, appropriate dose selection, and adherence to evidence-based dose constraints. CONCLUSIONS: The Radiosurgery Society's case-based practice review offers guidance to practicing physicians treating technically challenging SBRT candidate patients with spinal metastases.

A Case-based Guide for World Health Organization (WHO) Grade 2 Meningioma Radiosurgery and Radiation Therapy from The Radiosurgery Society.

PURPOSE: Meningiomas represent the most common primary tumor of the central nervous system. Current treatment options include surgical resection with or without adjuvant radiation therapy (RT), definitive RT, and observation. However, the radiation dose, fractionation, and margins used to treat patients with WHO grade 2 meningiomas, which account for approximately 20% of all meningiomas, are not clearly defined, and deciding on the optimal treatment modality can be challenging owing to the lack of randomized data. METHODS AND MATERIALS: In this manuscript, 3 cases of patients with WHO grade 2 meningiomas are presented with descriptions of treatment options after gross total resection, subtotal resection, and previous irradiation. Treatment recommendations were compiled from 9 central nervous system radiation oncology and neurosurgery experts from The Radiosurgery Society, and the consensus of treatment recommendations is reported. RESULTS: Both conventional and stereotactic RT are treatment options for WHO grade 2 meningiomas. The majority of prospective data in the setting of WHO grade 2 meningiomas involve larger margins. Stereotactic radiosurgery/hypofractionated stereotactic RT are less appropriate in this setting. Conventionally fractionated RT to at least 59.4 Gy is considered standard of care with utilization of preoperative and postoperative imaging to evaluate the extent of disease and possible osseous involvement. After careful discussion, stereotactic radiosurgery/hypofractionated stereotactic RT may play a role for the subset of patients who are unable to tolerate the standard lengthy conventionally fractionated treatment course, for those with prior RT, or for small residual tumors. However, more studies are needed to determine the optimal approach. CONCLUSIONS: This case-based evaluation of the current literature seeks to provide examples for the management of grade 2 meningiomas and give examples of both conventional and stereotactic RT.

SBRT for Pancreatic Cancer: A Radiosurgery Society Case-Based Practical Guidelines to Challenging Cases.

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions.

Scalp Irradiation with 3D-Milled Bolus: Initial Dosimetric and Clinical Experience.

BACKGROUND AND PURPOSE: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. MATERIALS AND METHODS: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0-69.96). RESULTS: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25-90%). The median dose homogeneity index was 1.07 (range: 1.03-1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0-75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. CONCLUSIONS: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

The Radiosurgery Society Case-Based Discussion of the Management of Head and Neck or Skull Base Paragangliomas with Stereotactic Radiosurgery and Radiotherapy.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used for the treatment of head and neck or skull base paraganglioma for a considerable time, demonstrating promising local control rates and a favorable safety profile compared with surgical approaches. Nevertheless, the choice of treatment must be carefully tailored to each patient's preferences, tumor location, and size, as well as anticipated treatment-related morbidity. This case-based review serves as a practical and concise guide for the use of SRS and FSRT in the management of head and neck or skull base paragangliomas, providing information on the diagnosis, treatment, follow-up considerations, and potential pitfalls.

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases.

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Stereotactic Body Radiation Therapy for Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients. METHODS AND MATERIALS: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a framework for treatment of similar patients. RESULTS: Treatment of gynecologic malignancies with SBRT requires many considerations, including treatment intent, optimal patient selection, fractionation selection, tumor localization, and plan optimization. Although other treatment paradigms including conventionally fractionated radiation therapy and brachytherapy remain the standard-of-care for definitive treatment of gynecologic malignancies, SBRT may have a role in palliative cases or those where high doses are not required due to the unacceptable toxicity that may occur with SBRT. CONCLUSIONS: A case-based practice review was developed by the Radiosurgery Society to provide a practical guide to the common scenarios noted above affecting patients with gynecologic malignancies.

Experience with intraoperative radiation therapy in an urban cancer center.

BACKGROUND/OBJECTIVE: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. METHODS: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. RESULTS: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months). CONCLUSIONS: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. TRIAL REGISTRATION: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT.

BACKGROUND: A nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA. METHODS: Between 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan-Meier methods and predictors of outcomes using multi-variable cox regression model. RESULTS: In the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972-9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference. CONCLUSION: In HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

Disease Burden on PET Predicts Outcomes for Advanced NSCLC Patients Treated with First-Line Immunotherapy.

BACKGROUND: First-line immunotherapy (IMT), with or without cytotoxic chemotherapy, is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no targetable mutations. We reviewed outcomes for NSCLC patients treated with first-line IMT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET/CT have prognostic value. MATERIALS AND METHODS: Patient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Numbers of extrathoracic lesions and metabolic tumor volumes were tabulated. Oligometastatic disease (OMD) was defined as having ≤3 extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IMT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and logrank tests. RESULTS: One hundred twenty-four patients met inclusion criteria, and 1143 lesions were contoured. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months; P = .016) and favorable OS (median 36.5 vs. 15.4 months; P = .002). In multivariable models, OMD was associated with favorable PFS (HR = 0.64; P = .034) and favorable OS (HR = 0.61; P = .063), and metabolic tumor volumes exceeding the cohort median (88 cc) was associated with inferior OS (HR = 1.85; P = .028). CONCLUSION: For advanced NSCLC patients receiving first-line IMT, the presence of extrathoracic OMD and low volumetric disease burden on PET are favorable prognostic factors that could be useful stratification factors in clinical trials and may influence clinical decisions about local and systemic therapy.

Additional therapy improves outcomes in completely resected, limited-stage follicular lymphoma.

Patients with early-stage nodal follicular lymphoma (FL) may be rendered free of detectable disease by a diagnostic excisional biopsy. We reviewed the management and outcomes of 48 patients with FL, diagnosed from 2003-2013, treated at a single institution. The primary endpoints were local control (LC) and progression-free survival (PFS).Median age at diagnosis was 54.5 years (range 15-74 years). Forty-seven patients were stage I (97.9%); 15 patients (31.3%) had grade 3 disease. Initial management consisted of observation (12 patients; 25.0%), radiation therapy (RT) alone (12 patients; 25.0%), systemic therapy alone (9 cases; 18.8%), or both (15 patients; 31.3%). Median follow-up was 4.92 years (range 0.5-13.83 years). 4-year PFS and OS were 80.9% and 97.1%, respectively. Patients treated with additional therapy experienced significantly better 4-year LC (100% vs. 81.8%; p = .012) and 4-year PFS (86.7% vs. 63.6%; p = .006).Patients with completely resected limited-stage FL would benefit from therapy beyond excisional biopsy alone.

Prognostic significance of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase-1 (IDH-1) mutation in glioblastoma multiforme patients: A single-center experience in the Middle East region.

OBJECTIVES: To determine the prevalence and prognostic value of MGMT promoter methylation and IDH1 mutation in glioblastoma multiforme (GBM) patients from the Middle East. PATIENTS AND METHODS: Records of patients diagnosed between 2003 and 2015 were reviewed. MGMT promoter methylation was measured using methylation-specific polymerase chain reaction and IDH-1 mutation was reported. The primary endpoint was overall survival (OS). RESULTS: A total of 110 patients were included. The median age was 51 years and 71 patients (64.5%) were males. The median diameter of GBM was 4.6 cm and 29 patients (26.4%) had multifocal disease. Gross total resection was achieved in 38 patients (24.9%). All patients received adjuvant radiation therapy, and 96 patients (91.4%) received concomitant temozolomide. At a median follow up of 13.6 months, the median OS was 17.2 months, and the OS at 1 and 2 years were 71.6% and 34.8%, respectively. On multivariate analysis, age at diagnosis (HR 1.019; P = 0.044) and multifocality (HR 2.373; P = 0.001) were the only independent prognostic variables. MGMT promoter methylation was found in 28.2% of patients but did not significantly correlate with survival (HR 1.160; P = 0.635). IDH-1 mutation was found in 10% of patients was associated with a non-significant trend for survival improvement (HR 0.502; P = 0.151). CONCLUSION: Patients with GBM from the Middle East have adequate survival outcomes when given the optimal treatment. In our patient population, MGMT promoter methylation did not seem to correlate with outcomes, but patients with IDH1 mutation had numerically higher survival outcomes.

Limited stage grade 3 follicular lymphoma patients can experience favorable outcomes with combined modality therapy.

Controversy exists regarding the optimal management of limited stage grade 3 follicular lymphoma (FL3). We assessed the treatment outcomes of 190 consecutive patients with stage I-II FL. Fifty two patients had FL3 disease, in whom the median age was 55 years. At a median follow-up of 65 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 76.6% and 87.6%, respectively. Patients receiving systemic therapy followed by radiation therapy (RT) had a significantly better PFS (p=.003) than those treated with RT alone, but similar OS (p = .476). Patients treated with RT had 100% local control. Compared to 132 patients with grade 1-2 FL, those with FL3 had similar PFS (p = .493) and OS (p = .330). Patients with FL3 can experience favorable outcomes when treated with a combination of systemic therapy and RT, comparable to low grade FL.

Early Stage Extranodal Follicular Lymphoma: Characteristics, Management, and Outcomes.

INTRODUCTION: Extranodal follicular lymphoma (E-FL) is a rare entity that has distinct characteristics and outcomes compared with nodal follicular lymphoma. PATIENTS AND METHODS: This cohort comprised 37 patients with stages I/II E-FL, diagnosed from 2003 to 2013. Outcomes included progression-free survival (PFS), and overall survival (OS). Survival outcomes were calculated using Kaplan-Meier methods. RESULTS: Median age was 60 years (range, 37-84 years). Disease was stage I in 29 (78.4%). The Follicular Lymphoma International Prognostic Index score was 0 to 1 in 31 (83.8%), 2 in 2 (5.4%), 3 in 1 (2.7%), and missing in 3 (8.1%). Sites of involvement included the gastrointestinal (GI) tract in 22 (59.5%), and non-GI sites in 15 (40.5%). Initial management consisted of chemotherapy (CHT) alone in 21 (56.8%), radiation therapy (RT) alone in 2 patients (5.4%), RT and rituximab in 1 (2.7%), CHT and RT in 7 (18.9%), and observation in 6 (16.2%). RT was to a median dose of 30.6 Gy (range, 23.4-44.0 Gy). At a median follow-up of 69 months (range, 8-157 months), 5-year PFS and OS were 70.4% and 94.4%, respectively. Although the 5-year PFS of those observed was worse than for those who received therapy (33.3% vs. 77.6%; P = .011), that did not translate into an OS difference. Patients who received RT as part of upfront management had a 100% local control (LC) rate and a trend toward improved 5-year PFS (90% vs. 62.2%; P = .067). CONCLUSION: Early stage E-FL is an indolent disease and is associated with excellent OS. Treatment strategies should be individualized with RT prioritized when LC is a significant goal.

Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG.

PURPOSE: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.

Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides.

BACKGROUND AND PURPOSE: A lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT). METHODS AND MATERIALS: We identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort. RESULTS: 71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395-0.290, p < 0.001). CONCLUSION: Peripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation.

Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.